Transient peaks in zinc and metallothionein levels during differentiation of 3T3L1 cells

A novel role for zinc mediated by metallothionein (MT) is found in the proc ess of differentiation of 3T3L1 mouse fibroblasts to adipocytes. Twenty-fou r hours after the stimulation of differentiation by hormones, the cells ent er into a phase of synchronous proliferation. In this phase the cellular co ntents of zinc and metallothionein rise rapidly to fivefold and threefold l evels, respectively. Simultaneously MT is translocated from the cytoplasm t o the nucleus. The rise of intracellular zinc is essential for the transiti on from G(0)/G(1)- to S-phase of the cell cycle. Deprivation ok zinc with N ,N,N ',N '-tetrakis[2-pyridyl]ethylenediamine membrane-permeable zinc chela tor, inhibited hormonal induced proliferation. After the short phase of pro liferation a slower stage of actual differentiation to adipocytes begins. T he elevated levels of MT and zinc decline quickly to start levels, and a ra pid redistribution of MT to the cytoplasm occurs. We propose that the nucle ar translocation of MT mediates the transfer of zinc to nuclear factors in the mitogenic process. The redistribution of MT to the cytoplasm and the de crease of the zinc content are postulated to be required for the start of t he actual differentiation. (C) 1999 Academic Press.